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This Week in Nature: Jul 19, 2012

Members of The Cancer Genome Atlas team this week present a molecular characterization of 276 colorectal carcinoma samples; the researchers analyzed the samples' exome sequence, DNA copy number, and promoter methylation as well as mRNA and microRNA expression. "A subset of the colorectal tumors — most often those turning up in the right or ascending colon — had unusually high mutation levels. And more than three-quarters of these hypermutated samples showed enhanced methylation levels and microsatellite instability," our sister publication GenomeWeb Daily News reports. "For the most part, though, the researchers found that colorectal carcinomas carried the same sorts of genetic glitches when they originated in colon as when they appeared in rectal tissue." Study co-author Raju Kucherlapati tells our sister publication Pharmacogenomics Reporter that he and his colleagues found two genes, ERBB2 and IGF2, that were amplified in a significant proportion of samples they analyzed. This suggested to them that "about 5 percent of patients might be candidates for treatment with either Roche/Genentech's Herceptin, in the case of ERBB2; or with the 20 percent for IGF2-targeted therapies currently in development," PGX Reporter adds. Daily Scan's sister blog Cancer Minute also has more on this study.

In another Nature advance online publication, a team led by investigators at the Dana-Farber Cancer Institute in Boston tests "the hypothesis that genomic variations and tumor viruses may cause cancer through related mechanisms, by systematically examining host interactome and transcriptome network perturbations caused by DNA tumor virus proteins." Using this approach, the team says it found a "rewiring of the host cell networks," which highlighted pathways that go awry in cancer. "We show that systematic analyses of host targets of viral proteins can identify cancer genes with a success rate on a par with their identification through functional genomics and large-scale cataloguing of tumor mutations," the Dana-Farber-led team writes.

Researchers at the University of Wisconsin-Madison and Stanford University report on an RNAi screen in Caenorhabditis elegans, in which they identified the heritable RNAi defective 1 — or hrde-1 — gene, which "encodes an Argonaute protein that associates with small interfering RNAs in the germ cells of progeny of animals exposed to double-stranded RNA," they write. "Under normal growth conditions, HRDE-1 associates with endogenously expressed short interfering RNAs, which direct nuclear gene silencing in germ cells," the researchers add. "In hrde-1- or nuclear RNAi-deficient animals, germline silencing is lost over generational time."

Over in Nature Methods, MIT's Daniel Marbach and his colleagues discuss the Dialogue on Reverse Engineering Assessment and Methods project, or DREAM, and how it has established "establish community-based methods as a powerful and robust tool for the inference of transcriptional gene regulatory networks."

The Scan

Long COVID-19 Susceptibility Clues Contained in Blood Plasma Proteome

A longitudinal study in eBioMedicine found weeks-long blood plasma proteome shifts after SARS-CoV-2 infection, along with proteomic signatures that appeared to coincide with long Covid risk.

Tibetan Study Finds Adaptive Variant Influencing Skin Pigmentation

With a combination of phenotyping and genetic data, researchers document at PNAS a Tibetan-enriched enhancer variant influencing melanin synthesis and ultraviolet light response.

Domestication Linked to Nervous System Genes in Inbred Mouse Strains

Researchers highlighted more than 300 positively selected genes in domesticated mice, including genes linked to nervous system function or behavior in Genome Biology.

ALS Genetic Testing May Be Informative Across Age Ranges, Study Finds

Researchers in the journal Brain identified clinically actionable variants in a significant subset of older ALS patients, prompting them to point to the potential benefits of broader test use.